CN103505462B - The purposes of 20 (S)-protopanoxadiols - Google Patents
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Abstract
The present invention relates to the novelty teabag of 20 (S)-protopanoxadiols, be specially 20 application of (S)-protopanoxadiol in the medicine preparing prevention and therapy ischemic heart desease, the myocardiac histology damage that 20 (S)-protopanoxadiols can reduce ischemia and ischemia-reperfusion and cause is found by pharmacodynamic study, reduce the Enzyme target that infarct size is relevant to myocardial necrosis, the displacement of electrocardiogram J point is reduced.
Description
Technical field
The present invention relates to the novelty teabag of 20 (S)-protopanoxadiols, specifically, relate to 20 application of (S)-protopanoxadiol in the medicine preparing prevention and therapy ischemic heart desease.
Background technology
In China, cardiovascular disease has become (comprising hypertension and coronary heart disease) principal disease of harm humans health and lives.2002, China's big city resident's deaths from heart disease rate reached 75.68/10 ten thousand people, is only second to malignant tumor, cerebrovas-cularaccident, occupies the cause of death the 3rd.
Myocardial ischemia heart disease is also known as coronary heart disease (coronaryheartdisease), refer to because coronary atherosclerosis makes luminal stenosis or obstruction cause myocardial ischemia or anoxia and the heart disease caused, for coronary atherosclerosis causes the most common type of organ lesion.Clinical manifestation is stable angina pectoris, unstable angina pectoris, arrhythmia, cardiogenic shock etc.Wherein unstable angina pectoris can develop into acute myocardial infarction (AMI) and even dies suddenly.
Coronary heart disease is called as " number one killer " in developed country, and in developing country, sickness rate is also more and more higher.World Health Organization (WHO) (WHO) predicts, will become the cause of the death that beats the world to the year two thousand twenty cardiovascular disease.
The treatment of current coronary heart disease, mainly contains these three kinds of means of Drug therapy, interventional therapy and bypass surgery.Wherein, Drug therapy is the most basic treatment, can be divided into 9 groups such as calcium channel blocker, disease treatment medication, peripheral vasodilators according to the ATC coding of WHO.
The treatment myocardial ischemia drug used clinically is mostly the medicines such as Folium Ginkgo, Alprostadil, amlodipine, Rhizoma Zingiberis Recens, fructose diphosphate, nifedipine, puerarin, isosorbide mononitrate, Herba Erigerontis, arasaponin, wherein use wider based on the cardiovascular drugs of Chinese medicine or Chinese medicine ingredients, its advantage is determined curative effect, side effect is little, because cognition degree improves constantly, so market potential is huge.
In Cardiac valve replacement process, need to give cardioplegic solution to patient, set up extracorporeal circulation, after aorta is blocked, can myocardial ischemia be caused.After aorta is open, Myocardial Ischemia Reperfusion Injury can be caused.
Protopanoxadiol is the interior metabolism product of glycol group ginsenoside, protopanoxadiol is divided into be divided into 20-(S) protopanoxadiol (20 (s)-protopanaxadiol, 20 (S)-dammarane-24-alkene-3 β, 12 β, 20-triol) and 20 (R)-protopanoxadiols (20 (R)-protopanaxadiol, 20 (R)-dammarane-24-alkene-3 β, 12 β, 20-triol), they are enantiomer each other, and its structure is as follows:
20-(S) protopanoxadiol 20-(R) protopanoxadiol
Patent CN200910139993.X, discloses protopanaxadiol-type's saponin in Radix Notoginseng for atherosclerosis.
Patent CN03132958.6 discloses 20 (R)-ginsenoside-RG3 to be prepared and is preventing the application in the medicine of cardiovascular and cerebrovascular disease.
By up to the present, not yet about the patent report of 20 (S)-protopanoxadiol treatment myocardial ischemia heart disease aspects.
Document aspect: Guo Yucheng, Tang Xudong etc. report the activation that Radix Notoginseng total arasaponins can suppress NF-B in neutrophilic granulocyte, reduce ICAN-1 and express and neutrophil infiltration, thus improve Myocardial Microcirculation and play the effect (Guo Yucheng of myocardial preservation, Tang Xudong, Gu great Yong, Jiang great Chun, Jiang Jianqing, Radix Notoginseng total arasaponins is to the experimentation of myocardial ischemia reperfusion injury protective effect, J.ofChineseNierocireulationOct, 2004, Vo1.8.No.5); Jin Ming; Qu Shaochun reports american ginseng glycol saponin injection (IPQDS) and has obvious protective effect to myocardial ischemia-reperfusion injury; may with its enhancing activities of antioxidant enzymes; reduce the oxidative damage of radical pair cardiac muscle; reduce endogenous vaso-active substance ET and AngII release; correct the unbalance mechanism that waits of PGI2/TXA2 about (gold inscription; Qu Shaochun; Yu little Feng, Xu Huali, used as a personal name in ancient times high-ranking official; the impact of american ginseng glycol saponin Injection in Rats myocardial ischemia reperfusion injury; Tianjin Chinese medicine, Apr.2006, Vo1.23No.2).Wu Shufang etc. report Panax quinquefolium 20 s-protopanaxdiol Saponins Antiarrhythmic Effect and mechanism thereof (Wu Shufang etc. Panax quinquefolium 20 s-protopanaxdiol Saponins Antiarrhythmic Effect and mechanism thereof, Chinese Pharmaceutical Journal, 02 phase in 2002)
Although above-mentioned research has pointed out saponins compound for reperfusion injury of cardiac muscle there being potential protective effect, above-mentioned research has been all mixture of multiple saponins compound, fails to point out specifically which saponin compound role.Secondly, the myocardium protecting action of these compounds all only just can be observed under larger dosage, namely in body effective dose all at more than 100mg/kg.Due to glycol saponins oral after can promptly be converted to various metabolite in vivo, comprise Rg3, Rh2, compound-K and PPD, these metabolites and protopanoxadiol saponins have significantly different in mechanism, and its myocardium protecting action also has no report.
Summary of the invention
The object of this invention is to provide the novelty teabag of 20-(S)-protopanoxadiol.
The invention provides 20-(the S)-application of protopanoxadiol in the medicine preparing prevention and therapy ischemic heart desease.
Described ischemic heart desease is selected from coronary heart disease or coronary atherosclerotic heart disease.
Preferably, ischemic heart desease of the present invention is myocardial ischemia and myocardial ischemia reperfusion injury.
Described myocardial ischemia and myocardial ischemia reperfusion injury are silent myocardial ischemia, angina pectoris, myocardial infarction, ischemic cardiomyopathy and/or sudden death.
Preferably, myocardial ischemia and myocardial ischemia reperfusion injury also comprise and to exercise heart due to treatment needs and suspend perfusion and the myocardial ischemia that causes of resuscitation and myocardial ischemia reperfusion injury again.
Described myocardial ischemia and myocardial ischemia-reperfusion also comprise the myocardial ischemia and myocardial ischemia reperfusion injury that Post operation causes, as cardiac valve replacement the myocardial ischemia that causes and myocardial ischemia reperfusion injury.
Above-mentioned application of the present invention, 20 (S)-protopanoxadiol preparations that 20 (S)-protopanoxadiols are made up of 20 (S)-protopanoxadiols and pharmaceutically acceptable carrier or adjuvant.
Described 20 (S)-protopanoxadiol preparations are injection, tablet, capsule, solution (oral), the agent of gas (powder) mist, patch, granule, Sublingual tablet or drop pill.
The invention has the advantages that:
1, disclose 20 (S)-protopanoxadiol groups (PQDS) in prior art to be obtained by the separation and purification of araliaceae ginseng plant's Folium Panacis Quinquefolii (PanaxquinquefoliumL.) leaf total saponins, main containing panaxdiols saponin Rb
1, Rb
2, Rb
3, Rd monomer component, share the purposes for the treatment of myocardial ischemia with other drug.Each monomer structure is as follows:
Ginsenoside Rd ginsenoside Rb1
Ginsenoside Rb3 ginsenoside Rb2
Compared with prior art, 20 (S)-protopanoxadiols that inventor studies are the metabolites in the body of glycol group ginsenoside, derive from prior art Material Source different, and structurally there are differences.
2, find by pharmacodynamic study the myocardiac histology damage that 20 (S)-protopanoxadiols can reduce ischemia and ischemia-reperfusion and cause, reduce the Enzyme target that infarct size is relevant to myocardial necrosis, the displacement of electrocardiogram J point is reduced, thus is that 20 (S)-protopanoxadiol preparations or compositions provide foundation for ischemic heart disease.
3, the medicine of cardiovascular disease easily occurs erythra, hemorrhage, arrhythmia, headache, dizzy etc. easily producing drug resistance and dependency at present.And 20 (S)-protopanoxadiols derive from plant material, production technology is simple, and cost is low, relative to other Cardiovarscular medicine, has side effect little, safe and reliable advantage.Therefore one of medicine that can be used as Cardiovarscular.
4, we find by experiment, and meanwhile, 20 (S)-protopanoxadiols also can be used for performing the operation the protection of the myocardial ischemia caused, and the peri-operation period of performing the operation for heart stopping collecting (extracorporeal circulation) etc. has the effect of myocardial preservation.And the derivant of 20 (S)-protopanoxadiols also show good activity for prevention and therapy ischemic heart desease.
Accompanying drawing explanation
Fig. 1: 20 (S)-protopanoxadiols (PPD) and Rb1 comparing the protective effect of the Cardiac Cells In Vitro of hydrogen peroxide treatment.The result of this experiment shows that PPD significantly will be better than ginsenoside Rb1 for the protection of myocardial cell.
Detailed description of the invention
Following examples for illustration of the present invention, but are not used for limiting the scope of the invention.
Experimental example 1: on the impact of the Cardiac Cells In Vitro of hydrogen peroxide treatment
In order to investigate metabolite 20 (S)-protopanoxadiol saponin (PPD) myocardial preservation function of protopanoxadiol saponins, this experiment has selected glycol saponins Rb1 main in protopanoxadiol saponins group to compare the protective effect of PPD and Rb1 to the Cardiac Cells In Vitro of hydrogen peroxide treatment.
1, test material
1.1 test samples: 20 (S)-protopanoxadiols (PPD), Rb1 provides by Shanghai Chinese Medicine Creation Research Center;
1.2 experimental apparatus:
Clean bench, Microcystins in The Dianshan Lake cleaning equipment factory;
Constant temperature CO
2incubator, Forma company of the U.S.;
Enzyme-linked immunosorbent assay instrument, BioTek company of the U.S.;
Inverted biological microscope, Chongqing optical instrument;
Desk-top constant-temperature table, Taicang science and education equipment factory.
1.3 experiment reagents: DMEM culture medium (GIBCO), trypsin GIBCO) hyclone (GIBCO), MTT (Sino-A-Biotel), DMSO (Chemical Reagent Co., Ltd., Sinopharm Group), DMSO (Sigma); Hydrogen peroxide (Chemical Reagent Co., Ltd., Sinopharm Group).
1.4 cell strains: cell strain provided by Chinese Academy of Sciences's cell.
H9C2 cell, is incubated in DMEM in high glucose culture medium, containing 15% calf serum, and 37 DEG C, 5%CO
2.
2, experimental technique:
With the H9C2 cell of In vitro culture, the protective effect of research PPD, Rb1 anti-peroxidation hydrogen damage, and compare its IC
50value.
2.1 get and are in one bottle, cell in good condition exponential phase of growth, make cell suspension.
2.2 cell countings, and cell density is diluted to 1 × 10
5individual/ml.
2.3 obtained cell suspensions are inoculated on 96 orifice plates, and 100 μ l/ holes, put constant temperature CO
2cultivate in incubator.
2.4 add above test-compound respectively, if blank, compound effects final concentration is respectively 0.1, and 0.5,1,2,5,10 μMs, the multiple hole of each concentration 3 is cultivated.
2.5 continue to add hydrogen peroxide, and every hole 10 μ l, final concentration is 100 μMs, cultivates in incubator.
2.6MTT PBS is made into 5mg/ml solution, is added by MTT in 96 orifice plates, 10 μ l/ holes, reacts after 4 hours and sucks supernatant, add DMSO150 μ l/ hole, continue to hatch, make resolution of precipitate in incubator.
2.7 is that 570nm place measures the light absorption value in every hole with enzyme-linked immunosorbent assay instrument at wavelength, and calculates inhibitory rate of cell growth and protected effect (reversion rate).
Inhibitory rate of cell growth %=(negative control group OD value-processed group OD value)/(negative control group OD value-blank group OD value) × 100%
2.8 each compounds in triplicate.
3, the results are shown in accompanying drawing 1:
Protopanoxadiol saponin Rb1 is better than significantly as can be seen from the effect of accompanying drawing 1: 20 (S)-protopanoxadiol (PPD) protection cardiac muscle.
Experimental example 2: on the impact of myocardial ischemia and Ischemia-Reperfusion Injury Model
For confirming that 20 (S)-protopanoxadiols are to the effect of myocardial preservation further, lower example is that 20 (S)-protopanoxadiols have carried out pharmacologic agent research to myocardial ischemia and ischemical reperfusion injury animal model.
1, test material
1.1 test sample
20 (S)-protopanoxadiols (PPD), are provided by Shanghai Chinese Medicine Creation Research Center; 20 (S)-protopanoxadiols are mixed with suspension in accordance with the following methods: take 100mg sample, add 10ml0.5%CMC-Na grinding, be mixed with 10mg/ml suspension
1.2 positive control sample
Title: Nifedipine Tablets, believe that friendship pharmacy head factory provides by Shanghai Pharmaceutical (Group) Co., Ltd., specification is: 10mg/ sheet, lot number: the accurate word H31021222 of traditional Chinese medicines; Character: Film coated tablets; Storage practice: room temperature preservation;
Preparation: adding 0.5%CMC-Na grinding after pulverizing, to be mixed with content be 2mg/ml suspension
1.3 other medicines
Urethane, lot number HG22-771-68, Cao Yang Second Middle School chemical plant, is made into 25% solution with normal saline.
2, experimental animal
SD rat, male and female half and half, body weight: 220-250 gram, purchased from Shanghai Si Laike laboratory animal responsibility company limited; The quality certification number: SCXK (Shanghai) 2002-0010
Rearing conditions: SPF level rat experiment receptacle, temperature: 23+1 DEG C, humidity: 40 ~ 70%, illumination: 12 hours light and shades are alternately.
Drinking-water: filtered water, freely drinks
Feedstuff: Mus full nutritious particle feedstuff, Songjiang Che Dun laboratory animal seed multiplication farm
Feeding manner: raise in cages
3, test apparatus
MP150systems, ECG100C amplifier, BIOPACsystemsInc., AcqKnowledgeVer3.9.0 process software;
722 grating spectrophotometers, Shanghai the 3rd analytical tool factory;
ALC-V8B animal artificial respirator, Alcott bio tech ltd, Shanghai.
4, test kit
NBT stain, lot number: 20071101, advance chemical reagent factory in Shanghai is produced;
Lactic acid dehydrogenase (LDH) testing cassete, acetone acid dinitrophenylhydrazone develops the color;
Creatine kinase (CK) testing cassete, molybdenum phosphate acid system;
Above testing cassete builds up Science and Technology Ltd. by Nanjing and produces.
5, experiment grouping
5.1 myocardial ischemia: (9 groups)
Sham operated rats: lumbar injection NS0.5m1/100g;
Model group:, lumbar injection NS0.5ml/100g;
Test group: 20 (S)-protopanoxadiol groups and 20 (S)-protopanoxadiol high dose group (being called for short PPD group and PPD high dose group), lumbar injection 25mg/kg/ day and 50mg/kg/ day respectively
Positive controls: nifedipine gastric infusion, dosage is 10mg/kg.
Said medicine except nifedipine, all according to administration volume 0.5ml/100g administration.
5.2 ischemia-reperfusions (five groups)
Sham operated rats: lumbar injection NS0.5ml/100g;
Model group: lumbar injection NS0.5ml/100g;
Test group: 20 (S)-protopanoxadiol groups and 20 (S)-protopanoxadiol high dose group (being called for short PPD group and PPD high dose group), lumbar injection 25mg/kg/ day and 50mg/kg/ day respectively
Positive controls: nifedipine, gastric infusion, dosage is 10mg/kg.
Said medicine except nifedipine, all according to administration volume 0.5ml/100g administration.
5.3 administration time
Successive administration 7 days before test, once a day; Myocardial ischemia respectively organizes last administration first 30 minutes of anesthesia ligation; Each group of ischemia-reperfusion is administered once in anesthesia ligation for first 30 minutes, gives once during Reperfu-sion again.
6, experimental technique
6.1 process of the test
Animal starts administration in 7 days before the test, once a day, and successive administration 7 days.Test last administration on the same day 30 minutes pneumoretroperitoneum injection urethane 1.2g/kg anesthesia, faces upward position and fixes, insert tracheal casing pipe, connect respirator, thrust extremity with needle electrode subcutaneous, measure II lead electrocardiogram, left 3-4 intercostal opens breast, expose heart, gently mention pericardium with ophthalmic tweezers, carefully tear, with (3*6 under left auricle, 3/8) round needle, No. 00000 silk thread.
Each group of myocardial ischemia (except sham operated rats), in arterial cone and coronary sulcus place ligation left coronary artery, is then sewed up and is closed breast chamber; Sham operated rats only threading not ligation, timing immediately, closes breast, removes respirator and recovers autonomous respiration.
Each group of ischemia-reperfusion (except sham operated rats) eyeless suture needle falls a underpass left front, line two is through a 1.5cm long diameter 1.5mm polyethylene tube, 3min post-tensioning suture the polyethylene tube pushed away outside line falls branch to block a coronary artery left side, timing immediately, close breast, remove respirator and recover autonomous respiration, ischemia recovers blood for filling with again after 1 hour, and administration again after Reperfu-sion.Within after ligation 3 hours, put to death animal, ventral aorta is taken a blood sample, centrifuging and taking Virus monitory LDH, CK index, observes the impact that given the test agent changes the Myocardial Enzymologic that myocardial ischemia causes.Core dirty carry out histology's (change of Infarct area) detect.
Before detecting ECG administration to record, after ligation 10,20,30 and 60 minutes, after Reperfu-sion 15,30,45,60 and the height of the Electrocardiographic ST section of 120min or J point, and carry out statistical analysis with the absolute value changed.
6.2 Testing index
The change of Rat Ecg T ripple, J point; Rat myocardial infarction model area; Serum creatine kinase (CK), lactic acid dehydrogenase (LDH).
7, experimental result:
7.1 impacts on infarct size: the results are shown in Table 1
Table 1: on the impact of permanent ischemia and myocardial ischemia reperfusion in rats infarct size
Note: compared with sham operated rats, * * * P < 0.001; Compare with negative control group
#p < 0.05,
##p < 0.01,
###p < 0.001.
Table 1 result shows:
Compared with sham operated rats, the infarct size of negative control group extremely significantly increases (P < 0.001);
Compared with negative control group, 20 (S)-protopanoxadiol intraperitoneal injection 50mg/kg bring out the obvious reducing effect of area (p < 0.05) of myocardial infarction to myocardial ischemia, and positive control nifedipine 10mg/kg also makes infarction decline (p < 0.01) significantly.
Compared with negative control group, 20 (S)-protopanoxadiol intraperitoneal injection 25mg/kg and 50mg/kg bring out the area reducing effect in various degree (p < 0.05 and p < 0.01) of myocardial infarction to myocardial ischemia-reperfusion, and the infarct size of nifedipine has significant difference (p < 0.01).
7.2 impacts on serum enzyme content: in table 2,3
Table 2: on the impact of permanent ischemia and ischemia-reperfusion rat blood serum LDH vigor
Note: compared with sham operated rats, * * * P < 0.001; Compare with negative control group
#p < 0.05,
##p < 0.01,
###p < 0.001.
Table 3: on the impact of permanent ischemia and ischemia-reperfusion rat blood serum CK vigor
Note: compared with sham operated rats, * * * P < 0.001; Compare with negative control group
#p < 0.05,
##p < 0.01,
###p < 0.001.
Table 2,3 result displays:
Consistent with histology result, the serum enzyme content that negative control group is relevant to myocardial necrosis has the rising of highly significant, the difference highly significant (p < 0.01) that LDH and CK vigor raises compared with sham operated rats, LDH and the CK vigor after myocardial ischemia and ischemia-reperfusion group 20 (S)-protopanoxadiol group intraperitoneal injection is all starkly lower than negative control group (p < 0.05).Positive drug nifedipine also significantly reduces LDH and the CK value of myocardial ischemia reperfusion injury animal serum, with 20 (S)-protopanoxadiol groups without significant difference.
7.3 impacts on ST section on electrocardiogram or J point:
7.3.1 the impact of the J point displacement of rats with myocardial ischemia: in Table 4-1
Table 4-1: on the impact (± s) of rats with myocardial ischemia J point displacement
Note: compared with sham operated rats, * * P < 0.01, * P < 0.05.
From the display of table 4-1 result:
Myocardial ischemia: the data that rat II leads ST section or the change of J point on electrocardiogram show, after negative control group myocardial ischemia, J point rises rapidly or declines, and reaches the highest, progressively declines later, comparatively sham operated rats significant difference to when 20 minutes; Each administration group J point declines with negative control group without significant difference.
7.3.2 on the impact of ischemia-reperfusion rat J point displacement: in Table 4-2
Table 4-2: on the impact of ischemia-reperfusion rat J point displacement
Note: compared with sham operated rats, * * P < 0.01, * P < 0.05; Compare with negative control group
#p < 0.05,
##p < 0.01.
Table 4-2 display: after ischemia-reperfusion group ligation, negative control group ST section or J point rise rapidly, higher than sham operated rats when 20 to 60 minutes, difference highly significant; After Reperfu-sion, the displacement of J point declines rapidly, and, higher than sham operated rats, there is significant difference 15 minutes and 120 minutes; 20 (S)-protopanoxadiol group high dose administrations before ligation, the displacement of J point when 20 minutes is significantly less than negative control group, is still less than negative control group, significant difference during to 60 minute the following; During Reperfu-sion, the J point displacement of 20 (S)-protopanoxadiol groups declines rapidly, but with negative control group difference nonsignificance; After positive control Nifedipine group makes ischemia 10-60 minute and fill with again latter 15 minutes the displacement of J point decline, with negative control group significant difference.
The incidence of arrhythmia no significant difference of each treated animal.
8, conclusion
20 (S)-protopanoxadiol intraperitoneal injections can reduce the myocardiac histology damage that ischemia and ischemia-reperfusion cause, and infarct size is reduced, the Enzyme target reduction relevant to myocardial necrosis, electrocardiogram J point displacement reduction.Its effect is slightly weak compared with the nifedipine of 10mg/kg.
The medicine of cardiovascular disease easily occurs erythra, hemorrhage, arrhythmia, headache, dizzy etc. easily producing drug resistance and dependency at present.And 20 (S)-protopanoxadiols derive from plant material, production technology is simple, and cost is low, relative to other Cardiovarscular medicine, has side effect little, safe and reliable advantage.Therefore one of medicine that can be used as Cardiovarscular.
The preparation method of embodiment 1:20 (S)-protopanoxadiol
1, Folium Notoginseng glycoside 5.0 kilograms, adds n-butyl alcohol, Sodium ethylate, inserts reactor, stirs, passes into oxygen, and keeping has bubble to emerge continuously in bubbling, heats up, reacts 72 hours; Add the saturated water washing of n-butyl alcohol twice after cooling, branch vibration layer, n-butyl alcohol concentrating under reduced pressure is recycled to dry, reclaims n-butyl alcohol, residue adds water stirring, extracts three times, water layer discarded by ethyl acetate, combined ethyl acetate layer, with saturated common salt water washing secondary, branch vibration layer;
2, in ethyl acetate layer, add anhydrous sodium sulfate, dry, ethyl acetate layer is evaporated to dry, reclaims ethyl acetate, obtains protopanoxadiol crude product;
3, in crude product, ethyl acetate is added, mixing, upper silicagel column, carry out column chromatography, use petroleum ether (60-90 DEG C)-ethyl acetate (3: 1) 200 liters and petroleum ether (60-90 DEG C)-ethyl acetate (1: 1) 500 liters of eluting successively, collect eluent, the composition of every part of eluent is monitored with TLC, one pack system eluent concentrating under reduced pressure, vacuum drying, obtains 20 (S)-protopanoxadiols.
Embodiment 2: 20 (S)-protopanoxadiol oral liquid
Tween 80 20g, soluble in water, add 20 (S)-protopanoxadiol 10g, colostrum is made in grinding, then adds water to 1000ml, obtains oral liquid.
Embodiment 3: 20 (S)-protopanoxadiol capsule
20 (S)-protopanoxadiol 10g, add lactose 300g, mixing, and with 70% ethanol for binding agent, granulate, incapsulate, obtain capsule, every containing 20 (S)-protopanoxadiol 50mg.Embodiment 4: 20 (S)-protopanoxadiol sheet
20 (S)-protopanoxadiol 10g, add lactose 300g, mixing, with 70% ethanol for binding agent, granulate, dry, and add magnesium stearate, tabletting, obtain tablet, every sheet is containing 20 (S)-protopanoxadiol 50mg.
Embodiment 5: 20 (S)-protopanoxadiol injection
20 (S)-protopanoxadiol 10g, sodium chloride 100g, 1000ml water for injection is dissolved in dilute preparing tank, and after stirring, cooling, decolouring, filtration, sterilizing, sealed cans, obtain injection.
Although above with general explanation, detailed description of the invention and test, the present invention is described in detail, and on basis of the present invention, can make some modifications or improvements it, this will be apparent to those skilled in the art.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, all belong to the scope of protection of present invention.
Claims (7)
1.20 application of (S)-protopanoxadiol in the medicine preparing prevention and therapy ischemic heart desease, described ischemic heart desease is selected from myocardial ischemia and myocardial ischemia reperfusion injury.
2. application according to claim 1, is characterized in that, myocardial ischemia and myocardial ischemia reperfusion injury are silent myocardial ischemia, angina pectoris, myocardial infarction, ischemic cardiomyopathy and/or sudden death.
3. application according to claim 1, is characterized in that, myocardial ischemia and myocardial ischemia reperfusion injury also comprise to exercise heart and suspend perfusion and the myocardial ischemia that causes of resuscitation and myocardial ischemia reperfusion injury again due to treatment needs.
4. application according to claim 1, is characterized in that, myocardial ischemia and myocardial ischemia reperfusion injury also comprise the myocardial ischemia and myocardial ischemia reperfusion injury that cardiac valve replacement causes.
5. the application according to claim 1-4 any one, it is characterized in that, 20 (S)-protopanoxadiol preparations that 20 (S)-protopanoxadiols are made up of 20 (S)-protopanoxadiols and pharmaceutically acceptable carrier or adjuvant.
6. application according to claim 5, is characterized in that, 20 (S)-protopanoxadiol preparations are selected from injection, tablet, capsule, oral liquid, aerosol, patch, granule or drop pill.
7. application according to claim 6, is characterized in that, described preparation is Sublingual tablet.
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| PCT/CN2013/076347 WO2013189229A1 (en) | 2012-06-19 | 2013-05-28 | New use of 20(s)-protopanoxadiol |
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| CN114832025B (en) * | 2022-05-17 | 2023-09-05 | 杭州医学院 | Preparation method and application of ginseng adventitious root crude extract |
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| WO2006113495A2 (en) * | 2005-04-15 | 2006-10-26 | Hui-Ling Chen | Dicarboxylic acid ester derivatives of ginsenoside, pharmaceutical preparations containing the same, and preparation thereof |
| CN102018716A (en) * | 2009-09-14 | 2011-04-20 | 王泽君 | Medical application of protopanaxatriol and protopanaxadiol in nervous system diseases |
| CN102311474A (en) * | 2010-07-07 | 2012-01-11 | 北京师范大学 | Method for preparing protopanaxadiol and protopanaxatriol by solvent-free method |
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| WO2006113495A2 (en) * | 2005-04-15 | 2006-10-26 | Hui-Ling Chen | Dicarboxylic acid ester derivatives of ginsenoside, pharmaceutical preparations containing the same, and preparation thereof |
| CN102018716A (en) * | 2009-09-14 | 2011-04-20 | 王泽君 | Medical application of protopanaxatriol and protopanaxadiol in nervous system diseases |
| CN102311474A (en) * | 2010-07-07 | 2012-01-11 | 北京师范大学 | Method for preparing protopanaxadiol and protopanaxatriol by solvent-free method |
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| CN103505462A (en) | 2014-01-15 |
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